Characteristics of patients with atrial fibrillation treated with direct oral anticoagulants and new insights into inappropriate dosing: results from the French National Prospective Registry: PAFF.

AIMS: Since the introduction of direct oral anticoagulant (DOAC) for atrial fibrillation (AF) therapy, inappropriate and/or underdosing of these drugs has been a major clinical challenge. We evaluated the characteristics of patients with AF treated with inappropriate and low-dose DOACs. METHODS AND RESULTS: Patients with AF treated with inappropriate and low-dose DOACs from October 2021 to December 2021 were evaluated from the French National Prospective Registry (PAFF). We evaluated 1890 patients with AF receiving DOACs (apixaban 55%, dabigatran 7%, and rivaroxaban 38%). Inappropriate dosing was noted in 18% of the population. Patients with appropriate dosing had less comorbidities: younger age (75 ± 10 vs. 82 ± 8 years old, P < 0.0001), reduced chronic renal failure (26 vs. 61%, P < 0.0001), and lower CHA2DS2VASc and HASBLED scores (3 ± 2 vs. 4 ± 3, P < 0.0001; 2 ±1 vs. 2 ± 2, P < 0.0001), respectively. In multivariate analysis, older age (P < 0.0001) and a higher CHA2DS2VASc score (P = 0.0056) were independently associated with inappropriate DOAC dosing. Among 472 patients (27%) treated with low-dose rivaroxaban or apixaban, 46% were inappropriately underdosed. Patients inappropriately underdosed were younger (82.3 ± 8.4 vs. 85.9 ± 5.9 years, P < 0.0001) with less chronic renal disease (47 vs. 98%, P < 0.0001). However, these patients had higher rates of prior haemorrhagic events (18 vs. 10%, P = 0.01), clopidogrel use (11 vs. 3%, P = 0.0002), and apixaban prescription (74 vs. 50%, P < 0.0001). CONCLUSION: Within this large registry, DOACs were associated with inappropriate dosing in 18% of cases. Independent predictors of inappropriate dosing were high CHA2DS2VASc scores and older age. Moreover, 46% of patients treated with low-dose DOACs were inappropriately underdosed and more frequently in patients treated with apixaban.

Review Article: Gastrointestinal Bleeding Risk with Direct Oral Anticoagulants.

PURPOSE: Although direct oral anticoagulants (DOACs) are associated with an overall favourable safety profile, the risk of gastrointestinal bleeding with DOACs compared with vitamin K antagonists (VKAs) remains controversial. Accordingly, we aimed to provide a focused overview of the risk of gastrointestinal bleeding associated with dabigatran, rivaroxaban, apixaban and edoxaban and its management. METHODS: We reviewed published studies reporting on DOACs with gastrointestinal bleeding as an outcome, including randomised controlled trials (RCTs), retrospective database studies and large-scale prospective cohort studies. RESULTS: Cumulative evidence confirms no notable difference in major gastrointestinal bleeding risk between DOACs and VKAs. Moreover, gastrointestinal bleeding in DOAC-treated patients seems less severe and requires less intensive management. The main cause of upper gastrointestinal bleeding in DOAC-treated patients appears to be gastroduodenal ulcers, whereas lower gastrointestinal bleedings are mainly due to diverticula followed by angiodysplasia and haemorrhoids. The lack of head-to-head RCTs with DOACs precludes drawing conclusions on the DOAC with the lowest gastrointestinal bleeding risk. Prescribing physicians should be aware of risk factors for DOAC-related gastrointestinal bleeding (e.g. age > 65, heavy alcohol use, uncontrolled hypertension, hepatic or renal dysfunction, active cancer, anaemia) and adopt preventive measures accordingly. Management of DOAC-associated major gastrointestinal bleeding involves temporary discontinuation of the DOAC, investigation of the bleeding source and treatment of bleeding with fluid resuscitation combined with transfusion and endoscopic haemostasis. CONCLUSION: DOACs as a class do not increase the risk of major gastrointestinal bleeding compared to VKAs, which supports their continued use for different anticoagulant indications.

Hydroxychloroquine and azithromycin tolerance in haemodialysis patients during COVID-19 infection.

BACKGROUND: Haemodialysis patients are at risk of developing severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: coronavirus disease 2019 (COVID-19). In March 2020, hydroxychloroquine (HCQ) and azithromycin (AZI) were proposed as potential treatments of COVID-19, but with warnings concerning their possible toxicity. No data are available regarding the toxicity of this treatment in haemodialysis patients. METHODS: We report the use of HCQ and AZI in a cohort of COVID-19 haemodialysis patients with focus on safety concerns. RESULTS: Twenty-one patients received 200 mg HCQ thrice daily during 10 days, and AZI 500 mg on Day 1, and 250 mg on the four following days. HCQ plasma concentrations were within the recommended range (0.1-1.0 µg/mL) in all patients except one, in which maximum concentration was 1.1 µg/mL. HCQ concentration raised until the third day and remained stable thereafter. No cardiac event occurred in spite of progressive lengthening of corrected QT interval (QTc) during the treatment. One patient experienced a long QTc syndrome (QTc >500 ms) without any arrhythmia episode, although HCQ concentration was in the target range. Five (23.8%) patients experienced hypoglycaemia, a well-known HCQ side-effect. SARS-CoV-2 RNA remained detectable in nasopharyngeal swabs for a long time in haemodialysis patients (mean time 21 days). CONCLUSIONS: HCQ and AZI are safe in haemodialysis patients at these doses but can lead to long QTc syndrome and hypoglycaemia. HCQ concentrations were not correlated with side effects. We recommend monitoring of the QTc length throughout treatment, as well as glycaemia. SARS-CoV-2 could persist for longer in haemodialysis patients than in the general population.

Reduction of procedure duration and radiation exposure with a dedicated inner lumen mapping catheter during pulmonary vein cryoablation.

BACKGROUND: The Achieve catheter (AC; Medtronic-CryoCath, Pointe-Claire, Canada) is a circular mapping catheter introduced through the lumen of the cryoballoon (CB) catheter which is safe and effective to both navigate the CB to the pulmonary veins (PV) and allow PV potential recording during PV cryoablation. The aim of this study was to evaluate the impact of the use of the AC on procedural outcomes. METHODS: Sixteen consecutive patients (14 men) underwent AC-guided PV isolation (PVI) for drug-refractory paroxysmal atrial fibrillation (AF; AC group). Clinical and procedural data of these patients were compared to those obtained from 16 consecutive patients who had undergone PVI for paroxysmal AF with the regular "single transseptal" approach (control group). RESULTS: Clinical characteristics of patients enrolled in both groups did not differ significantly. In the AC group, 64 PVs were targeted using a single 28-mm (n = 13) or 23-mm (n = 3) CB catheter with PVI achieved in 62 PVs (97%). In the control group, 66 PVs were targeted using a single 28-mm (n = 12) or 23-mm (n = 4) CB catheter with PVI achieved in 62 PVs (94%), (P = non-significant for CB size and PVI rate). Procedure duration and fluoroscopy time were significantly reduced in AC group compared to control group (96.6 ± 26 minutes vs 125.9 ± 25 minutes, P = 0.003 and 24.4 ± 10 minutes vs 32.6 ± 11 minutes, P = 0.04, respectively). CONCLUSION: The use of the AC significantly reduced procedure duration and radiation exposure during PVI with the CB technique.

Management of antithrombotics in situations with a gap in evidence: A national French survey focusing on patients with coronary artery disease and atrial fibrillation.

BACKGROUND: If several randomized studies allowed to better apprehend what should be the best antithrombotic strategy in patients with concomitant coronary artery disease (CAD) and atrial fibrillation (AF), there are still several clinical situations with a gap of evidence. METHODS: We conducted a national French survey in September-October 2020 among cardiologists in order to assess what are daily practices regarding the antithrombotic management in several specific clinical settings where no or little scientific evidence is available. The questionnaires were built by a committee of 6 cardiologists routinely involved in the field of CAD and/or AF. RESULTS: Among the 6388 French cardiologists, 483 (7.6%) cardiologists participated to the survey. The rate of participation was rather homogeneous across the country. The mean age of participants was 48 +/- 12.7. There were 134 women (27.7%) and 349 men. Altogether, 181 (37.5%) cardiologists worked in private, 153 (31.7%) in non-universitary public and 83 (17.2%) in universitary public centers. The remaining had shared activity. Among the participants, 150 were interventional (coronary) cardiologists (31.1%). Others were general cardiologists (n = 229), specialists in the field of rhythmology (n = 43), heart failure (n = 17) or imaging (n = 44). The survey consisted of 10 questions pertaining to 2 virtual clinical scenarios. CONCLUSIONS: The present survey is an illustration of how therapeutic decisions may vary in such situations with little or no scientific evidence. Such surveys may help experts to build consensus (answers with little variability) and to target the need for future trials and more research (answers with a lot of variability).

Management of outpatients in France with stable coronary artery disease. Findings from the prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY) registry.

BACKGROUND: Improvements in the treatment of coronary artery disease mean that an increasing number of patients survive acute cardiovascular events and live as outpatients with or without anginal symptoms. AIM: To determine the characteristics and management of contemporary outpatients with stable coronary artery disease in Western Europe, and to compare France with the other Western European countries. METHODS: CLARIFY (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an international, prospective, observational, longitudinal study. Between November 2009 and July 2010, 32,954 adult outpatients with stable coronary artery disease (defined as a history of documented myocardial infarction [of >3 months], prior coronary revascularization, chest pain with myocardial ischaemia, or coronary stenosis of>50% proven by angiography) were enrolled in 45 countries. The demographics and management of CLARIFY patients enrolled in France were compared with those enrolled in other Western European countries (Austria, Belgium, Denmark, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland and the UK). RESULTS: Of the 14,726 patients enrolled in Western Europe (mean age 66.2 [10.2] years; 79.6% male), 2432 (16.5%) were from France. The use of aspirin was lower in France than in other Western European countries (74.5% vs. 86.9%, respectively), whereas use of thienopyridines (48.5% vs. 21.7%), oral anticoagulants (12.3% vs. 9.0%) and lipid-lowering drugs (95.8% vs. 92.5%) was higher. Beta-blockers were used in 73% of both groups. Angina was less prevalent in France (6.3% vs. 15.5%) and French patients showed higher levels of physical activity than their counterparts in Western Europe. CONCLUSIONS: The management of patients with stable CAD in France appears favourable, with good adherence to guideline-based therapies, but there remains room for improvement in terms of symptom and risk factor control.

Ambulatory hypertensive patients treated by cardiologists in France.

BACKGROUND: While general practitioners treat most hypertensive patients in France, hypertension is the most frequent pathology treated by cardiologists, raising questions about the differing profiles of such patients. Poor control of hypertension is commonly reported, and yet has not improved over time. Better understanding of the determinants of control, at both patient and physician levels, is necessary to implement improvements in practice. AIMS: To describe the hypertensive population treated by independent cardiologists in France and to assess the prevalence and determinants of not-at-goal blood pressure (BP), at patient and physician levels. METHODS: The COLHYGE study was an observational cross-sectional epidemiological study. Consecutive patients (n=5798) were selected by 371 independent cardiologists in France. Data concerning patients and physicians were assessed. RESULTS: Our study population had an elevated cardiovascular risk, high prevalence of patients in secondary cardiovascular prevention (27.5%) and a high proportion of diabetic patients (22.8%). Only 20.8% of the population presented controlled BP. At the patient level, the following variables were negatively and independently associated with BP control: age; body mass index; heart rate; recently diagnosed hypertension; left ventricular hypertrophy; patient belief that they are taking too many pills; prescription of calcium channel blockers, lipid-lowering agents and antiplatelet agents. Presence of atrial fibrillation and the prescription of renin-angiotensin system blockers and fixed combinations correlated positively with BP control. At the physician level, working in big cities and having an exclusive independent practice were associated with good BP control. There was high heterogeneity among physicians in terms of BP control, independent of the patient and physician characteristics assessed. CONCLUSION: The COLHYGE study has confirmed a high cardiovascular risk and poor BP control among hypertensive patients treated by cardiologists in France. Strategies aiming to control BP should focus on both patient and physician characteristics.

Pulmonary vein isolation using a single size cryoballoon chosen according to transesophageal echocardiography information.

BACKGROUND: Pulmonary vein isolation (PVI) using cryoballoon (CB) catheter is a new technique for atrial fibrillation (AF) ablation. Previous studies used computer tomography (CT) or magnetic resonance imaging (MRI) scan to determine the pulmonary vein (PV) diameter and anatomy for choosing the CB size. We evaluated pre-ablation transoesophageal-echocardiography (TEE) as an alternative to CT/MRI scan in patients undergoing AF ablation for determining the appropriate size of the CB. METHODS: Fifty-five consecutive patients (men=43, women=12) with a mean age of 63 ± 12.5 years, and with drug-refractory paroxysmal AF (34 patients) or persistent AF (21 patients) were included in this prospective study. All patients underwent pre-ablation TEE. RESULTS: Hypertension was present in 19 patients (34%). Mean anterior-posterior left atrium diameter was 45.1 ± 8.9 mm. In total, 217 PV were targeted using a single 23-mm (n=14) or 28-mm (n=40) CB catheter chosen according to TEE-obtained measurements. PVI was achieved in 195 PV (90%). Mean number of CB applications per patient was 9.8 ± 2.1 (range 8-14). Mean procedure duration and fluoroscopy times were 131 ± 27 min (90-190 min) and 36 ± 12 min (22-66 min) respectively. Phrenic nerve palsy occurred in 3 patients (5.4%) and was transient (<1 month) in all of them. CONCLUSION: This study suggests that TEE is an easily available and effective tool to select the size of the CB for PVI according to evaluated PV diameters and anatomy.

Slow pathway elimination for atrioventricular nodal reentrant tachycardia with the 8-mm tip cryoablation catheter: an 18-month follow-up study.

PURPOSE: The 9-French 8-mm tip cryoablation catheter confers a high rate of acute slow pathway (SP) elimination and an acceptable short-term outcome in patients with atrioventricular nodal reentrant tachycardia (AVNRT). The aim of this study was to investigate the long-term outcome of patients treated with this electrode in this indication. METHODS: Eighty-two patients (female = 52) with a mean age of 54.9 ± 17.7 years underwent SP elimination for typical AVNRT with the 8-mm tip cryocatheter in our institution between November 2009 to June 2012. Clinical and procedural characteristics were prospectively collected. RESULTS: Acute procedural success defined as AVNRT non-inducibility at the end of the procedure was obtained in 81/82 patients (98.7 %). Mean procedure duration and fluoroscopy time were 74.4 ± 28.7 min (range, 35-160 min) and 8.7 ± 5.3 min (range, 2-26 min), respectively. Mean number of energy applications was 4.0 ± 2.4 (range, 2-15). No permanent atrioventricular block was observed. Transient atrioventricular block occurred in 12 patients (14.6 %). Traumatic fast pathway conduction block occurred in one patient before cryoenergy delivery. Using an intention-to-treat analysis, 78 patients (95.1 %) remained free of AVNRT recurrence during a mean follow-up of 17.8 ± 9.3 months. CONCLUSIONS: This study confirmed that the 8-mm tip cryocatheter is both safe and highly effective for SP conduction elimination in patients with AVNRT and demonstrated a low recurrence rate during a long-term follow-up.

Gender-related differences in the management of hypertension by cardiologists: the PARITE study.

BACKGROUND: Several studies have shown gender differences in the management of cardiovascular risk factors and diseases. Whether the management of hypertension by cardiologists in France differs according to patient gender has not been fully investigated. AIMS: The main objective of this cross-sectional, multicentre study was to examine the management according to gender of hypertensive patients by office-based cardiologists in France. METHODS: Cardiologists were asked to include consecutively two men and two women attending a routine consultation for essential hypertension. Therapeutic management was evaluated by comparing cardiovascular investigations in the preceding 6 months and hypertension control according to gender and the patients' global cardiovascular risk. RESULTS: Overall, data from 3440 adult patients (53% men) referred to 654 cardiologists were analysed. Hypertension was uncontrolled in 76% of both men and women and 69% were at high global cardiovascular risk (75% of men, 62% of women; P<0.001). Significantly fewer cardiovascular investigations had been performed in the preceding 6 months in women (22.6% vs 44.2% in men; P<0.001). The treatment regimen was changed by the cardiologist in approximately 50% of patients regardless of gender or global cardiovascular risk. CONCLUSIONS: The PARITE study shows that in French office-based cardiology practice, the antihypertensive regimen is adjusted as often in female as in male patients. However, the results suggest that there is room for improvement in the investigation of cardiovascular disease in women. Healthcare providers could be encouraged to implement established guidelines on the prevention of cardiovascular disease in women.

Distribution of left ventricular ejection fraction and heart rate values in a cohort of stable coronary patients: the INDYCE registry.

BACKGROUND: The distribution of left ventricular ejection fraction (LVEF) - a key factor in coronary artery disease (CAD) patient management and prognostication - is poorly documented. OBJECTIVE: To determine LVEF and heart rate (HR) values, and describe the management of stable CAD patients in France. METHODS: The INDYCE survey was a prospective, multicentre registry of consecutive stable CAD outpatients attending a cardiology consultation. The survey focused on LVEF values measured using the echocardiographic Simpson biplane method. Drug therapy, resting HR, blood pressure and symptoms were also recorded. RESULTS: Overall, 3119 patients (68.4 +/- 11.0 years; 80% men) were enrolled. LVEF was 56.1+/-11.8% on average, and was poor (<40%) and moderately impaired (40-50%) in 9.6% (n=298) and 19.8% (n=619) of cases, respectively. Symptomatic angina pectoris was present in 19.2% of cases and only 40.6% of patients were asymptomatic (no angina and NYHA class < or = I) despite relatively aggressive management (79.0% of patients had undergone coronary angioplasty and/or bypass graft). Interestingly, 14.1% of patients with LVEF less than 40% were asymptomatic. In multivariable analysis, LVEF less than 40% was associated most strongly with symptomatic status (odds ratio 3.82; 95% CI 2.59-5.63; P<0.0001), together with female sex, age greater than 75 years, diabetes, HR greater or equal to 70 bpm, sedentariness, obesity and disease duration. CONCLUSION: Only 9.6% of stable CAD patients had severe left ventricular dysfunction; among them, 14.1% were strictly asymptomatic. This could justify regular LVEF measurement in CAD patients. Three potentially reversible factors (HR>or=70 bpm, being overweight and sedentariness) were linked independently to the presence of symptoms.

Cross-ventricular pacemaker-mediated tachycardia by myopotential induction during biventricular pacing.

BACKGROUND: Patients in permanent atrial fibrillation treated for heart failure and ventricular asynchrony can be implanted with conventional dual chamber pacemakers (DDD) pacemakers used in the biventricular mode. The left ventricular lead is connected to the atrial channel. CASE REPORT: We report the case of a patient who developed ventriculo-ventricular pacemaker-mediated tachycardia (PMT) induced by myopotential sensing in the atrial channel, inhibiting left ventricular pacing. CONCLUSION: In the absence of specifically designed pacemakers, the use of DDD pacemakers in the biventricular mode requires certain precautions, such as anti-PMT mode activation, disabling automatic sensitivity, and lengthening the postventricular atrial refractory period (PVARP), or mode switch to DVIR.